Antimycobacterial N-pyridinylsalicylamides, isosters of salicylamides

The series of derivatives of substituted N-pyridinylsalicylamides were synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. In the quantitative structure activity relationships analysis (QSAR), the Free-Wilson and Hansch approaches were used but the analysis was not significant. (The standard deviations of regression coefficients were greater than the values of the coefficients). The molecules were separated the heterocyclic and salicyl moiety in the molecules, and the study of influences of substituents on salicyl moiety was used, as well. 5-chloro-pyridin-2-yl, and the substitution of the salicyl moiety by chlorine in position 4 or 5 had the strongest influence on the increase in antimycobacterial activity.     

Heterocyclic isosters of antimycobacterial salicylanilides

A series of 64 derivatives of substituted heterocyclic analogues of salicylanilides was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. For the QSAR study, the combination of Free-Wilson approach with Hansch approach was used. The molecules were separated on the heterocyclic and salicyl moieties and the study of influences of electronic and hydrophobic properties was used as well. The compounds are a new group of potential anti-tuberculotics.     

Antimycobacterial beta-aminoketones

Antimycobacterial β-Aminoketones Synthesis and testing for antimycobacterial properties (M. tuberculosis H 37 Ra) of the β-aminoketones 1-12 are described. These compounds combine the modes of action of N-alkyl-benzylamines and 3-(dimethylamino)ketones and show higher activities.     

Antimycobacterial antihistaminics

The testing of antihistaminic compounds of various chemical classes for antimycobacterial properties is described. A lot of these compounds inhibit the growth of mycobacteria at a concentration of 8-32 micrograms/ml.     

Synthesis and evaluation of the analgesic and antiinflammatory activities ofO-Substituted salicylamides

The present investigation deals with the synthesis of some new salicylamidoacetyl sulfonamides 3a,b, salicylamido ethylacetate 4, salicylamido acetic acid hydrazide 5, which is considered as the key intermediate for the synthesis of several series of new compounds such as salicylamido pyrazol 6 and pyrazolone 7. N-imido-derivatives 9, 10, 11, thiadiazole 13, oxadiazole 14, 15, Schiffs bases 16a-f. Cyclocondensation of Schiffs bases with thioglycolic acid gave thiazolidinone 18a-c while with acetylchloride afforded azitidinones 19a-c and with acetic anhydride gave 1,4-benzoxazepine-3,5-dione. Some of the compounds were tested for their analgesic and antiinflammatory activities as well as ulcerogenic effects. Some derivatives were more effective than salicylamide and ulcerogenic activity was variably lowered.     

Substituted Xanthones as Antimycobacterial Agents,Part 2: Antimycobacterial Activity

A series of substituted xanthones was tested for their activity against four mycobacterial strains (Mycobacterium tuberculosis, M. avium, M. lufu, M. smegmatis) by determination of the minimum inhibitory concentrations (MIC values). For the most active compounds, supplementary characterisation was performed by bacterial growth kinetics, which allows a more precise interpretation of their antimycobacterial effects. From the test set, 1-methyl-2,4,7-trinitroxanthone ( 8a ) showed the highest antimycobacterial activity with a MIC value of 3 μg/mL against M. tuberculosis, which is comparable to the effect of well known drugs used in the treatment of tuberculosis. For all other compounds, the MIC values could not be determined, due to the comparatively low activity and to the poor solubility of the compounds, respectively. The semiquantitative evaluation of activity against the different strains of mycobacteria resulted in a classification into three activity classes, which will be used as dependent parameter in QSAR investigations, to be published in Part 3 of this series.     

Synthesis and evaluation of the analgesic and antiinflammatory activities of N-substituted salicylamides

Some N-heterocyclic salicylamide derivatives were prepared by fusion of phenyl salicylate and heterocyclic amines, whereas other ones were synthesized by ring closure using N-salicyloyl-N'-anthranylhydrazine as starting material. All the compounds were tested for their analgesic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effects, in order to ascertain if the N-substitution would offer any advantages. Some derivatives were more effective than salicylamide and ulcerogenic activity was variably lowered.     

1-Aryl-N2-alkyl-ethanediamines as isosters of adrenergic arylethanolamines

A family of 1-aryl-N2-alkyl-ethanediamines 1 isosteric with the N-alkyl-arylethanolamines are described. Although the prepared compounds were generally less potent than the N-alkyl-arylethanolamines, the 1-aryl-N'-(phenylmethyl)-N-alkyl-1,2-ethanediamines derivatives 6, are more active than the debenzylated free amino analogs 1, which may be indicative of the importance of the lipophilicity of the substituent at the alpha position to the aromatic ring.     

Antimycobacterial plant terpenoids.

Abstract.Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis, is the leading killer among all infectious diseases worldwide and is responsible for more than two million deaths annually. For over thirty years no antitubercular agents with new mechanisms of action have been developed. The recent increase in the number of multi-drug resistant clinical isolates of M. tuberculosis has created an urgent need for the discovery and development of new antituberculosis leads. This review covers recent reports on plant-derived terpenoids that have demonstrated moderate to high activity in in vitro bioassays against M. tuberculosis. In this review, mono-, sesqui-, di- and triterpenes, and sterols, their structural analogs and semisynthetic derivatives will be discussed, with particular emphasis on the structural features essential for antimycobacterial activity.     

Antimycobacterial Activity of Taxus baccata

Crude extracts prepared from various parts of Taxus baccata L. have been evaluated for their antimycobacterial activity. A CHCl₃ fraction of the heartwood and ethanol extract of the leaves exhibited a minimum inhibitory concentration value (MIC) against Mycobacterium tuberculosis H₃₇Ra strain of 200?µg/ml.     

Antimycobacterial properties of antihistaminic compounds

Antimycobacterial Properties of Antihistaminic Compounds The testing for antimycobacterial properties (M. tuberculosis H 37 Ra, Middlebrook-7H9-broth) of the antihistaminic compounds 1–15 is described. These compounds are specific growth inhibitors of Mycobacterium tuberculosis H 37 Ra.     

Antimycobacterial arylidenecyclohexanones and related Mannich bases

Several series of 2-arylidenecyclohexanones and related Mannich bases as well as various 2,6-bis(arylidene)cyclohexanones were evaluated against Mycobacterium tuberculosis H37Rv. Using a concentration of 12.5 microg/ml, nearly half of the unsaturated ketones inhibited the growth of the microorganism by 21-66% while all of the Mannich bases achieved 99% or greater inhibition. The relative hydrophobicities and widths of the molecules may have been contributing factors as to whether bioactivity was present or absent. Two of the Mannich bases demonstrated noteworthy potencies towards Mycobacterium avium. The conclusion was drawn that Mannich bases of 2-arylidenecyclohexanones represent a novel class of antimycobacterials.     

Effects of remoxipride and some related new substituted salicylamides on rat brain receptors

A number of potential neuroleptic drugs of the substituted benzamide type have been compared with some reference neuroleptic drugs regarding their affinities for rat brain receptors using in vitro receptor binding techniques. The effects on dopamine-stimulated adenylate cyclase were also investigated. All 6-methoxysalicylamides were very potent inhibitors of the dopamine-D2 receptor and possessed much less affinity for other receptors as well as for the dopamine-stimulated adenylate cyclase. In contrast, the classical neuroleptic drugs were not selective dopamine-D2 receptor blockers. Several of these neuroleptics were thus potent inhibitors of alpha 1-receptors, 5-HT2 receptors, muscarinic receptors and histamine-H1 receptors. Sulpiride was the most selective dopamine-D2 receptor blocker of the reference compounds with a selectivity ratio of 65. The 6-methoxysalicylamides had selectivity ratios ranging from 18 to 167.     

Antimycobacterial and Antibacterial Activity of Allium sativum Bulbs

Tuberculosis is one of the major public health problems faced globally. Resistance of Mycobacterium tuberculosis to antitubercular agents has called for an urgent need to investigate newer drugs to combat tuberculosis. Garlic (Allium sativum) is an edible plant which has generated a lot of curiosity throughout human history as a medicinal plant. Garlic contains sulfur compounds like allicin, ajoene, allylmethyltrisulfide, diallyltrisulfide, diallyldisulphide and others which exhibit various biological properties like antimicrobial, anticancer, antioxidant, immunomodulatory, antiinflammatory, hypoglycemic, and cardiovascular effects. According to various traditional systems of medicine, garlic is one of the established remedies for tuberculosis. The objective of the current study was to investigate in vitro antimycobacterial activity as well as anti-bacterial activity of various extracts rich in specific phytoconstituents from garlic. Preparation of garlic extracts was done based on the chemistry of the constituents and their stability. The estimation of in vitro antimycobacterial activity of different garlic extracts was done using Resazurin microtire plate assay technique whereas activity of garlic oil was evaluated by colony count method. The antibacterial activity of extracts and oil was estimated by zone of inhibition method. Extracts of garlic rich in allicin and ajoene showed appreciable antimycobacterial activity as compared to standard drugs. Garlic oil demonstrated significant antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus.     

Antimycobacterial activity of 1-substituted indolizines

Indolizine derivatives were tested as antimycobacterials against Mycobacterium tuberculosis H(37)Rv (ATCC 27294)in BACTEC 12B medium using the Microplate Alamar Blue Assay. The most active compounds examined carry an alpha-hydroxybenzyl substituent in the indolizine 1-position. MICs against Mycobacterium tuberculosis for these compounds were 6.25 microg/mL     

抗肺结核药物研究进展

由于艾滋病和细菌耐药性的出现，结核病日益成为全球健康关注问题。目前迫切需要新的化学治疗药物。本文介绍一些具有抗结核分支杆菌活性的新化合物，如氟喹诺酮、恶唑烷酮、烷磺基乙酰胺和硝基咪唑类化合物的研究进展。